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, 21 (18), 3587-95

Ontological Analysis of Gene Expression Data: Current Tools, Limitations, and Open Problems

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Ontological Analysis of Gene Expression Data: Current Tools, Limitations, and Open Problems

Purvesh Khatri et al. Bioinformatics.

Abstract

Independent of the platform and the analysis methods used, the result of a microarray experiment is, in most cases, a list of differentially expressed genes. An automatic ontological analysis approach has been recently proposed to help with the biological interpretation of such results. Currently, this approach is the de facto standard for the secondary analysis of high throughput experiments and a large number of tools have been developed for this purpose. We present a detailed comparison of 14 such tools using the following criteria: scope of the analysis, visualization capabilities, statistical model(s) used, correction for multiple comparisons, reference microarrays available, installation issues and sources of annotation data. This detailed analysis of the capabilities of these tools will help researchers choose the most appropriate tool for a given type of analysis. More importantly, in spite of the fact that this type of analysis has been generally adopted, this approach has several important intrinsic drawbacks. These drawbacks are associated with all tools discussed and represent conceptual limitations of the current state-of-the-art in ontological analysis. We propose these as challenges for the next generation of secondary data analysis tools.

Figures

Fig. 1
Fig. 1
Evolution history of GO-based functional analysis software. The tool marked with a star has not been published in a peer-reviewed journal.
Fig. 2
Fig. 2
A speed comparison of the tools reviewed here. Four sets of 100, 200, 500 and 1000 human genes were submitted to each tool. The three fastest tools, GoSurfer, GeneMerge and Onto-Express, are all able to perform the analysis of up to 200 genes in under 8 seconds. Note that GOTM allows upload of only up to 500 genes.
Fig. 3
Fig. 3
Levels of abstraction. The analysis can be performed at a lowest level of abstraction (dash-and-dot line), at a fixed level of abstraction chosen by the user (dashed line) or at a custom level of abstraction that can go to different depths in various sub-trees of the GO (continuous line).

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